Colorectal cancer is the second leading cause of cancer deaths in the United States. According to the American Cancer Society, more than 130,000 Americans will be diagnosed with cancer of the colon or rectum this year. Fortunately researchers are making extraordinary progress in the development and/or identification of agents that may delay or prevent colorectal cancer. These include pharmaceuticals such as the non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs are effective at preventing polyp formation in familial adenomatous polyposis (FAP) patients having a genetic predisposition to cancer. Epidemiological evidence suggests that long-term NSAID use is associated with a decreased risk of colon cancer in non-familial colon cancer as well. However, NSAIDs can produce serious side effects including gastrointestinal bleeding and even death. One strategy to minimize toxicity of NSAIDs is to use very low doses in combination with other agents having complementary modes of action. Tea prevents intestinal and/or colorectal cancer in a variety of animal models and may be a suitable alternative or complement to NSAID therapy. Our preliminary data shows that tea or a combination of tea plus the NSAID sulindac is highly effective at preventing the formation of tumors in Apc m/In mice. These mice have a mutation in Apc (same gene altered in FAP) and, like humans with FAP, are genetically predisposed to develQp large numbers of intestinal adenomas at an early age. This suggests that tea alone, or a combination of tea plus sulindac may be of benefit in treating humans with FAP. These studies will examine the benefits of tea and/or purified tea constituents plus NSAIDs as preventive agents towards colon cancer. The research proposed in this R21 will provide necessary preliminary data for use in subsequent R01 proposals on how dietary factors and pharmaceuticals interact in the prevention of cancer, and should help establish the primary investigator as an independent researcher.